The Pacific Biosciences PacBio RS sequencing system will be used for high-throughput DNA sequencing in applications demanding long-range sequence information at the scale of tens of kilobases. The technology and characteristics of this sequencing technology are notably different than for other sequencing methodologies. In particular, the ability to obtain long sequence reads affords several critical advantages for a number of applications, including (1) the sequencing of novel genomes, (2) EST and transcriptome characterization in organisms lacking a sequenced or well-mapped genome, (3) the analysis of alternative pre-mRNA splicing, (4) amplicon sequencing. In addition to longer read lengths, the PacBio sequencing technology also provides rapid turnaround time. The PacBio RS will be applied to a diverse array of NIH-funded projects as well as other projects of high relevance to biomedical science, including the characterization of multigene families involved in sensory perception; the elucidation of the patterns and mechanisms of alternative pre-mRNA splicing; the characterization of genomes of genetic and evolutionary models of human development and disease; an analysis of the genetic loci associated with cancer; and an investigation of the susceptibility of mammalian cells to nutritional ions and environmental toxins. There are currently no PacBio sequencers on the UC Berkeley campus. The proposed instrument would be located close to its users as part of the Coates Genome Sequencing Center, and managed as part of the unified campus-wide sequencing core facility and associated Computational Genomics Resource Laboratory. Acquisition of this instrument will support researchers pursuing these projects, which promise to illuminate the fundamental mechanisms underlying human biology and disease.